Positive affective reactions to pleasant life events are crucial to healthy life function and well- being. Conversely, pathological hedonic dysfunction involving loss of positive affect (anhedonia) and/or excessive negative affect (dysphoria) has devastating consequences for individuals with mood disorders. Therefore it is crucial to understand how brain affective mechanisms generate normal positive affect, and especially how brain mechanisms boost the positive intensity of hedonic impact. Our previous studies identified a specific neuroanatomical/neurochemical hedonic generating network that amplifies pleasure, measured as prototypical orofacial 'liking'reactions to the hedonic impact of sweetness, which have brain mechanisms and evolutionary origins shared by humans with other mammals. The pleasure-generating brain network contains anatomically distributed cubic-millimeter hotspots or subregions, within deep forebrain structures of nucleus accumbens and ventral pallidum. Those brain hotspots are uniquely able to generate hedonic enhancements of natural sensory pleasure, in response to specific neurochemical stimulation. Yet still unknown are the actual neuronal mechanisms within hotspots that generate hedonic enhancement. Also unknown are how the hedonic hotspots functionally cooperate together to generate pleasure as a circuit, or how they interact with larger regulatory brain circuits. The studies proposed here will use optogenetic techniques to identify the neuronal mechanisms inside hotspots of nucleus accumbens and ventral pallidum that generate hedonic enhancements impact. The studies will also identify circuit-level brain interactions that control the generation of positive affect, and ill investigate how dysfunction in hotspots produces pathological anhedonia and dysphoria.
Mood disorders such as depression or schizophrenia are devastating in part because patients lose capacity for normal pleasures in life (resulting in symptoms of anhedonia and dysphoria). Without normal pleasure capacity, patients become trapped in distress and unable to function in life. This research will identify the specific brain mechanisms and circuits that generate and boost natural pleasure reactions which are needed for mental health. It will also identify how particular brain dysfunction in those brain mechanisms causes pathological distress. Understanding how brain mechanisms and circuits generate pleasant emotional reactions will help provide better insights into how to alleviate depression and related mood disorders.
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